PXD001186-2

PXD001186 is an original dataset announced via ProteomeXchange.

Title	A role for CPT1A to prevent blood vessel permeability revealed by in depth proteomics
Description	Endothelial cells (ECs) line the inner wall of blood vessels and maintain vascular stability. Vascular stability alteration is a hallmark of pathologies such as cancer and thrombosis. A role for fatty acid oxidation (FAO) in this process is unknown. Integrating MS-proteomics and metabolic modeling revealed that FAO increases when ECs cultured on matrigel are assembled into a fully formed network. Inhibition of CPT1A in ECs, a limiting enzyme in FAO, results in disruption of this network. Acute CPT1A inhibition reduces cellular ATP levels and oxygen consumption, which can be restored replenishing the tricarboxylic acid cycle (TCAc). Phosphoproteomic changes upon acute CPT1A inhibition evoked those triggered by thrombin, a potent inducer of EC permeability through calcium signaling. Indeed, CPT1A inhibition increased EC permeability and vascular leakage, which were restored replenishing the TCAc or, partially, inhibiting calcium influx. Our study shows the possibility of altering FAO to interfere with ECs in diseases.
HostingRepository	PRIDE
AnnounceDate	2018-03-08
AnnouncementXML	Submission_2018-03-08_00:09:30.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sara Zanivan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2014-07-30 05:17:43	ID requested
1	2015-01-28 07:58:37	announced
⏵ 2	2018-03-08 00:09:32	announced	Updated publication reference for PubMed record(s): 25573745.
3	2024-10-22 04:06:44	announced	2024-10-22: Updated project metadata.

Patella F, Schug ZT, Persi E, Neilson LJ, Erami Z, Avanzato D, Maione F, Hernandez-Fernaud JR, Mackay G, Zheng L, Reid S, Frezza C, Giraudo E, Fiorio Pla A, Anderson K, Ruppin E, Gottlieb E, Zanivan S, Proteomics-based metabolic modeling reveals that fatty acid oxidation (FAO) controls endothelial cell (EC) permeability. Mol Cell Proteomics, 14(3):621-34(2015) [pubmed]

curator keyword: Biomedical

submitter keyword: SILAC, label-free, FAO, CPT1A, human, endothelial cells

Sara Zanivan
contact affiliation	CRUK Beatson Institute
contact email	s.zanivan@beatson.gla.ac.uk
lab head
Sara Zanivan
contact affiliation	Vascular Proteomics
contact email	s.zanivan@beatson.gla.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2015/01/PXD001186

PRIDE project URI

• PRIDE
  1. PXD001186
     1. Label: PRIDE project
     2. Name: A role for CPT1A to prevent blood vessel permeability revealed by in depth proteomics